: Prenatal stress (PNS) is associated with increased biological risk for mental disorders such as anxiety and depression later in life, and stress appear to be additive to the PNS influences. Among the most widely cited and accepted alternative hypotheses of anxiety and depression is dysfunction of the HPA axis, a system that is central in orchestrating the stress response. Therefore, understanding how PNS exerts profound effects on the HPA axis and stress-sensitive brain functions including anxiety and depression has significant clinical importance. In this mini-review, we will focus on novel and evolving concepts regarding the potential mechanisms underlying the short and long-term effects of PNS involving CRH peptide family. We present evidence demonstrating prenatal hypoxia exposure induced anxiety-like behavior in adult male rat offspring and CRHR1 in PVN of the hypothalamus is involved.